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Myelin changes after spinal cord injury and throughout aging

Posted on:2010-11-07Degree:Ph.DType:Dissertation
University:University of WashingtonCandidate:Lasiene, JurateFull Text:PDF
GTID:1444390002978235Subject:Biology
Abstract/Summary:
The pattern of remyelination after traumatic spinal cord injury remains elusive. First, we wanted to establish the extent of demyelination on spared/intact axons. We found that spared and transporting rubrospinal tract (RST) axons were fully remyelinated exhibiting a marginally reduced myelin thickness and significantly shorter internodes while virally delivered GFP unveiled a small population of dystrophic RST axons with evident demyelination. Our mathematical model revealed that shorter internodes caused a 21% decrease in the conduction velocity. Next, we examined spared RST axons after SCI in a rat. Similar to the previous findings, we found extensively remyelinated RST axons by MBP positive oligodendrocytes with significantly shorter internodes. We also found axon diameters to be significantly smaller in injured animals. These data demonstrate the dynamic process of remyelination and how remarkably it is preserved among the species.;In our third study we investigated whether Neuregulin-1 type I and III proteins could positively modulate cytoarchitecture and myelin formation following SCI. After the delivery of the proteins for 14 days we found that type I did not have any anatomical effects while NRG1 type III significantly, albeit transiently, increased mitotic cell numbers and decreased the fraction of dividing cells immunopositive for progenitor marker NG2. Finally, NRG1 type III significantly yet transiently increased myelin thickness on axons caudal to the lesion epicenter. Our results demonstrate that infused NRG1 type III changes cytoarchitecture and myelin dynamics after SCI.;In our final study, we wanted to learn about myelin and glial cell proliferation dynamics created by normal aging not by trauma. We found that internode lengths significantly decrease in RST axons as a function of age, which suggests active remyelination. Next, we saw a decrease in gliogenesis in gray matter but an increase in white matter with aging. Half of newly generated cells expressed NG2 while most cells were positive for oligodendrocyte marker Olig2. Very few cells ever became positive for the astrocytic markers. These data demonstrate ongoing oligodendrogenesis and myelinogenesis as a function of age in the spinal cord.
Keywords/Search Tags:Spinal cord, Myelin, NRG1 type III, RST
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